Zonisamide (Zonegran)

Class

Sulfonamide anticonvulsant

Mechanism

Blocks voltage-gated sodium and T-type calcium channels, stabilizing neuronal membranes and reducing excitability

FDA-Approved Use

Adjunctive treatment of partial-onset seizures in adults with epilepsy

Off-Label Use

Augmentation in bipolar disorder, migraine prophylaxis, weight loss in obesity, management of impulsivity and aggression in traumatic brain injury (TBI) or neurodevelopmental disorders

Formulation

Oral capsules and tablets

Titration

Start at 50 mg p.o. daily, titrated gradually by 50–100 mg every 1–2 weeks based on response and tolerability

Dose Range

100–400 mg/day, usually once or twice daily

Kinetics

Half-life approximately 63 hours; metabolized hepatically (CYP3A4) and renally excreted; low protein binding

Common AEs

Fatigue, dizziness, nausea, anorexia, cognitive slowing, agitation

Serious/Rare AEs

Kidney stones, metabolic acidosis, oligohidrosis, Stevens-Johnson syndrome

Monitoring

Periodic monitoring of electrolytes, renal function, and serum bicarbonate levels

Black Box Warning

None

Considerations

Zonisamide may benefit patients with comorbid obesity, mood instability, or impulsivity related to TBI or neurodevelopmental disorders. Use caution in individuals with cognitive impairment, as word-finding difficulty and psychomotor slowing may occur. Avoid use in patients with sulfa allergy.